Study to Evaluate the Safety and Antiviral Activity of Inarigivir Soproxil (Formerly: GS-9992) Plus Tenofovir Alafenamide (TAF) for 12 Weeks in Adults With Chronic Hepatitis B (CHB)
- Registration Number
- NCT03434353
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objectives of this study are to evaluate the safety and tolerability of the 12 week treatment regimens of inarigivir soproxil plus tenofovir alafenamide (TAF) or commercially available nucleoside/nucleotide (NUC) in adults with chronic hepatitis B (CHB), to evaluate the antiviral activity of 12 weeks of inarigivir soproxil plus TAF versus TAF alone in viremic CHB participants (Groups 1-3, 5), and to evaluate the antiviral activity of 12 weeks of inarigivir soproxil with commercially available NUC(s) in virally suppressed CHB participants (Group 4).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 123
-
Groups 1-3 and 5:
- Individuals not taking any prescribed hepatitis B virus (HBV) NUC treatment
-
Group 4:
- HBV deoxyribonucleic acid (DNA) ≤ 20 IU/mL at Screening by Central Lab.
- Have been on a commercially available HBV NUC treatment(s)
Key
- Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV).
- Extensive bridging fibrosis or cirrhosis
- Evidence of hepatocellular carcinoma on imaging
- Any history of, or current evidence of, clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage).
- Chronic liver disease of a non-HBV etiology
- Current alcohol or substance abuse
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1: Inarigivir Soproxil 50 mg + TAF TAF Viremic participants will be administered inarigivir soproxil 50 mg (2 x 25 mg capsules) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed by TAF 25 mg tablet once daily orally with food for 36 weeks. Group 2: TAF TAF Viremic participants will be administered TAF 25 mg tablet once daily orally with food for 48 weeks. Group 5: Inarigivir Soproxil 400 mg + TAF TAF Viremic participants will be administered inarigivir soproxil 400 mg (2 x 200 mg tablets) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed TAF 25 mg tablet once daily orally with food for 36 weeks. Group 3: Inarigivir Soproxil 200 mg + TAF TAF Viremic participants will be administered inarigivir soproxil 200 mg (2 x 100 mg tablets) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed by TAF 25 mg tablet once daily orally with food for 36 weeks Group 5: Inarigivir Soproxil 400 mg + TAF Inarigivir Soproxil Viremic participants will be administered inarigivir soproxil 400 mg (2 x 200 mg tablets) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed TAF 25 mg tablet once daily orally with food for 36 weeks. Group 1: Inarigivir Soproxil 50 mg + TAF Inarigivir Soproxil Viremic participants will be administered inarigivir soproxil 50 mg (2 x 25 mg capsules) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed by TAF 25 mg tablet once daily orally with food for 36 weeks. Group 4: Inarigivir Soproxil 100 mg + commercially available NUCs Inarigivir Soproxil Virally suppressed participants receiving commercially available nucleoside/nucleotide (NUC) will be administered inarigivir soproxil 100 mg tablet once daily orally 1 hour before or 1 hour after a meal for 12 weeks. Participants will continue commercially available NUCs for 48 weeks. Group 3: Inarigivir Soproxil 200 mg + TAF Inarigivir Soproxil Viremic participants will be administered inarigivir soproxil 200 mg (2 x 100 mg tablets) once daily orally 1 hour before or 1 hour after a meal plus TAF 25 mg tablet once daily orally with food for 12 weeks followed by TAF 25 mg tablet once daily orally with food for 36 weeks
- Primary Outcome Measures
Name Time Method Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4) Baseline, Week 12 Percentage of Participants With ≥ 0.5 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1-3 and 5) Baseline, Week 12
- Secondary Outcome Measures
Name Time Method Change From Baseline in HBV DNA at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) Baseline, Weeks 12, 16, 24, 36, and 48 Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Groups 1 Through 3 and 5) Baseline, Week 12 Percentage of Participants With ≥ 1 log10 IU/mL Decline in HBsAg From Baseline at Week 12 (Group 4) Baseline, Week 12 Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) Baseline, Weeks 12, 24, 36, and 48 HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at post-baseline visit. Participants who had missing information were assumed to have no HBeAg loss.
Percentage of Participants Who Achieved HBsAg Loss at Weeks 12, 24, 36, and 48 (Group 4) Baseline, Weeks 12, 24, 36, and 48 HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at post-baseline visit.
Number of Participants With Sequence Changes From Baseline Within the HBV Polymerase for Participants Who Had HBV DNA ≥ 69 IU/mL (Groups 1 Through 3 and 5) Baseline, Week 48 Percentage of Participants Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough During 12 Weeks of Inarigivir Soproxil Treatment (Group 4) Baseline up to Week 12 Virologic breakthrough was defined as HBV deoxyribonucleic acid (DNA) ≥69 IU/mL for 2 consecutive visits
Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Groups 1 Through 3 and 5) Baseline, Weeks 12, 24, 36, and 48 HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at post-baseline visit. HBeAg seroconversion was defined as HBeAb changing from negative or missing at baseline to positive at any postbaseline visit. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion.
Percentage of HBeAg-positive Participants Who Achieved HBeAg Loss and Seroconversion at Weeks 12, 24, 36, and 48 (Group 4) Baseline, Weeks 12, 24, 36, and 48 HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at post-baseline visit. HBeAg seroconversion was defined as HBeAb changing from negative or missing at baseline to positive at any postbaseline visit. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion.
Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Groups 1 Through 3 and 5) Baseline, Weeks 12, 16, 24, 36, and 48 Change From Baseline in HBsAg at Weeks 12, 16, 24, 36, and 48 (Group 4) Baseline, Weeks 12, 16, 24, 36, and 48
Trial Locations
- Locations (13)
Catholic University of Korea, Seoul Saint Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Inje University Ilsan Paik Hospital
🇰🇷Ilsan, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
SMG-SNU Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
Kyungpook National University Hospital
🇰🇷Daegu, Korea, Republic of
Korea University Ansan Hospital
🇰🇷Ansan, Korea, Republic of
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
Gangnam Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Prince Margaret Hospital
🇭🇰Hong Kong, Hong Kong
Alice Ho Miu Ling Nethersole Hospital
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hospital-HK
🇭🇰Hong Kong, Hong Kong